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Childhood Bladder Cancer Treatment (PDQ®)–Health Professional Version

Clinical Presentation and Risk Factors

Urothelial bladder neoplasms are extremely rare in children. The most common presenting symptom of bladder cancer in children is hematuria.[1,2] Bladder tumors can present throughout the pediatric age range. In one small series, the mean age was 11.9 years (range, 4–19 years).[3] In another study, patients were aged between 16 months and 19 years. Most of the bladder tumors occurred in males.[4]

Bladder cancer in adolescents may develop as a result of exposure to alkylating-agent chemotherapy that was given to treat other childhood tumors or leukemia.[5-8] The association between cyclophosphamide exposure and bladder cancer is one of the only established relationships between a specific anticancer drug and a solid tumor.[9] An excess prevalence of bladder tumors has also been observed in survivors of specific cancer types (e.g., heritable retinoblastoma), supporting the concept that genetic factors contribute to the development of subsequent neoplasms.[10]

References
  1. Saltsman JA, Malek MM, Reuter VE, et al.: Urothelial neoplasms in pediatric and young adult patients: A large single-center series. J Pediatr Surg 53 (2): 306-309, 2018. [PUBMED Abstract]
  2. Rezaee ME, Dunaway CM, Baker ML, et al.: Urothelial cell carcinoma of the bladder in pediatric patients: a systematic review and data analysis of the world literature. J Pediatr Urol 15 (4): 309-314, 2019. [PUBMED Abstract]
  3. Galiya R, Stanislav K, Jawdat J, et al.: Pediatric urothelial bladder neoplasm. J Pediatr Urol 18 (6): 833.e1-833.e4, 2022. [PUBMED Abstract]
  4. Shumaker AD, Harel M, Gitlin J, et al.: Pediatric Bladder Tumors: A Ten-Year Retrospective Analysis. Urology 169: 185-190, 2022. [PUBMED Abstract]
  5. Di Carlo D, Ferrari A, Perruccio K, et al.: Management and follow-up of urothelial neoplasms of the bladder in children: a report from the TREP project. Pediatr Blood Cancer 62 (6): 1000-3, 2015. [PUBMED Abstract]
  6. Ritchey M, Ferrer F, Shearer P, et al.: Late effects on the urinary bladder in patients treated for cancer in childhood: a report from the Children's Oncology Group. Pediatr Blood Cancer 52 (4): 439-46, 2009. [PUBMED Abstract]
  7. Travis LB, Curtis RE, Glimelius B, et al.: Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma. J Natl Cancer Inst 87 (7): 524-30, 1995. [PUBMED Abstract]
  8. Kersun LS, Wimmer RS, Hoot AC, et al.: Secondary malignant neoplasms of the bladder after cyclophosphamide treatment for childhood acute lymphocytic leukemia. Pediatr Blood Cancer 42 (3): 289-91, 2004. [PUBMED Abstract]
  9. Johansson SL, Cohen SM: Epidemiology and etiology of bladder cancer. Semin Surg Oncol 13 (5): 291-8, 1997 Sep-Oct. [PUBMED Abstract]
  10. Frobisher C, Gurung PM, Leiper A, et al.: Risk of bladder tumours after childhood cancer: the British Childhood Cancer Survivor Study. BJU Int 106 (7): 1060-9, 2010. [PUBMED Abstract]

Histology

Histological classification of urothelial bladder neoplasms includes the following:

  • Urothelial papillomas.
  • Papillary neoplasms of low malignant potential.
  • Low-grade urothelial carcinomas.
  • High-grade urothelial carcinomas.

An alternative designation is transitional cell carcinoma of the bladder. The most common histology is papillary urothelial neoplasms of low malignant potential, while high-grade, invasive urothelial carcinomas are extremely rare in young patients.[1-5]

References
  1. Alanee S, Shukla AR: Bladder malignancies in children aged <18 years: results from the Surveillance, Epidemiology and End Results database. BJU Int 106 (4): 557-60, 2010. [PUBMED Abstract]
  2. Paner GP, Zehnder P, Amin AM, et al.: Urothelial neoplasms of the urinary bladder occurring in young adult and pediatric patients: a comprehensive review of literature with implications for patient management. Adv Anat Pathol 18 (1): 79-89, 2011. [PUBMED Abstract]
  3. Stanton ML, Xiao L, Czerniak BA, et al.: Urothelial tumors of the urinary bladder in young patients: a clinicopathologic study of 59 cases. Arch Pathol Lab Med 137 (10): 1337-41, 2013. [PUBMED Abstract]
  4. Di Carlo D, Ferrari A, Perruccio K, et al.: Management and follow-up of urothelial neoplasms of the bladder in children: a report from the TREP project. Pediatr Blood Cancer 62 (6): 1000-3, 2015. [PUBMED Abstract]
  5. Berrettini A, Castagnetti M, Salerno A, et al.: Bladder urothelial neoplasms in pediatric age: experience at three tertiary centers. J Pediatr Urol 11 (1): 26.e1-5, 2015. [PUBMED Abstract]

Treatment and Outcome of Childhood Bladder Cancer

Treatment options for childhood bladder cancer include the following:

  1. Surgery.

In contrast to adult bladder carcinomas, most pediatric tumors are low grade and superficial. Pediatric patients have an excellent prognosis after transurethral resection.[1-4] In one review of the literature, recurrence risk and mortality rates were low in pediatric patients (8.6% and 3.7%, respectively).[5] Most recurrences were observed within 9 months of treatment, and all recurrences occurred within 32 months of treatment. This finding suggests that patients should be monitored for at least 3 years.

Squamous cell carcinomas and more aggressive carcinomas have been reported in children and may require a more aggressive surgical approach.[3,6-8]

References
  1. Fine SW, Humphrey PA, Dehner LP, et al.: Urothelial neoplasms in patients 20 years or younger: a clinicopathological analysis using the world health organization 2004 bladder consensus classification. J Urol 174 (5): 1976-80, 2005. [PUBMED Abstract]
  2. Paner GP, Zehnder P, Amin AM, et al.: Urothelial neoplasms of the urinary bladder occurring in young adult and pediatric patients: a comprehensive review of literature with implications for patient management. Adv Anat Pathol 18 (1): 79-89, 2011. [PUBMED Abstract]
  3. Stanton ML, Xiao L, Czerniak BA, et al.: Urothelial tumors of the urinary bladder in young patients: a clinicopathologic study of 59 cases. Arch Pathol Lab Med 137 (10): 1337-41, 2013. [PUBMED Abstract]
  4. Berrettini A, Castagnetti M, Salerno A, et al.: Bladder urothelial neoplasms in pediatric age: experience at three tertiary centers. J Pediatr Urol 11 (1): 26.e1-5, 2015. [PUBMED Abstract]
  5. Rezaee ME, Dunaway CM, Baker ML, et al.: Urothelial cell carcinoma of the bladder in pediatric patients: a systematic review and data analysis of the world literature. J Pediatr Urol 15 (4): 309-314, 2019. [PUBMED Abstract]
  6. Sung JD, Koyle MA: Squamous cell carcinoma of the bladder in a pediatric patient. J Pediatr Surg 35 (12): 1838-9, 2000. [PUBMED Abstract]
  7. Lezama-del Valle P, Jerkins GR, Rao BN, et al.: Aggressive bladder carcinoma in a child. Pediatr Blood Cancer 43 (3): 285-8, 2004. [PUBMED Abstract]
  8. Korrect GS, Minevich EA, Sivan B: High-grade transitional cell carcinoma of the pediatric bladder. J Pediatr Urol 8 (3): e36-8, 2012. [PUBMED Abstract]

Treatment Options Under Clinical Evaluation for Childhood Bladder Cancer

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Special Considerations for the Treatment of Children With Cancer

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

  • Primary care physicians.
  • Pediatric surgeons.
  • Pathologists.
  • Pediatric radiation oncologists.
  • Pediatric medical oncologists and hematologists.
  • Ophthalmologists.
  • Rehabilitation specialists.
  • Pediatric oncology nurses.
  • Social workers.
  • Child-life professionals.
  • Psychologists.
  • Nutritionists.

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3-5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

  • A consensus effort between the European Union Joint Action on Rare Cancers and the European Cooperative Study Group for Rare Pediatric Cancers estimated that 11% of all cancers in patients younger than 20 years could be categorized as very rare. This consensus group defined very rare cancers as those with annual incidences of fewer than two cases per 1 million people. However, three additional histologies (thyroid carcinoma, melanoma, and testicular cancer) with incidences of more than two cases per 1 million people were also included in the very rare group due to a lack of knowledge and expertise in the management of these tumors.[9]
  • The Children's Oncology Group defines rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancers, melanomas and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinomas, nasopharyngeal carcinomas, and most adult-type carcinomas such as breast cancers and colorectal cancers).[10] These diagnoses account for about 5% of the cancers diagnosed in children aged 0 to 14 years and about 27% of the cancers diagnosed in adolescents aged 15 to 19 years.[4]

    Most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers diagnosed in children aged 0 to 14 years and 9.3% of the cancers diagnosed in adolescents aged 15 to 19 years.

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

References
  1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
  2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed August 23, 2024.
  3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
  4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed August 23, 2024.
  5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed September 5, 2024.
  6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
  7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
  8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
  9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
  10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children's Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

Latest Updates to This Summary (09/05/2024)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was comprehensively reviewed.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pediatric bladder cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Childhood Bladder Cancer Treatment are:

  • Denise Adams, MD (Children's Hospital Boston)
  • Karen J. Marcus, MD, FACR (Dana-Farber of Boston Children's Cancer Center and Blood Disorders Harvard Medical School)
  • William H. Meyer, MD
  • Paul A. Meyers, MD (Memorial Sloan-Kettering Cancer Center)
  • Thomas A. Olson, MD (Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta - Egleston Campus)
  • Alberto S. Pappo, MD (St. Jude Children's Research Hospital)
  • Arthur Kim Ritchey, MD (Children's Hospital of Pittsburgh of UPMC)
  • Carlos Rodriguez-Galindo, MD (St. Jude Children's Research Hospital)
  • Stephen J. Shochat, MD (St. Jude Children's Research Hospital)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Bladder Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/bladder/hp/child-bladder-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 31846271]

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Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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